Department of Biology, Institute of Genetics, University of Erlangen-Nürnberg, 91058 Erlangen, Germany.
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18772-7. doi: 10.1073/pnas.1111810108. Epub 2011 Nov 7.
Maintenance of immunological tolerance is crucial to prevent development of autoimmune disease. The production of autoantibodies is a hallmark of many autoimmune diseases and studies in mouse model systems suggest that inhibitory signaling molecules may be important checkpoints of humoral tolerance. By generating humanized mice with normal and functionally impaired Fcγ receptor IIB (FcγRIIB) variants, we show that the inhibitory Fcγ-receptor is a checkpoint of humoral tolerance in the human immune system in vivo. Impaired human FcγRIIB function resulted in the generation of higher levels of serum immunoglobulins, the production of different autoantibody specificities, and a higher proportion of human plasmablasts and plasma cells in vivo. Our results suggest that the inhibitory FcγRIIB may be an important checkpoint of humoral tolerance in the human immune system.
免疫耐受的维持对于预防自身免疫性疾病的发生至关重要。自身抗体的产生是许多自身免疫性疾病的标志，小鼠模型系统的研究表明，抑制性信号分子可能是体液免疫耐受的重要检查点。通过生成具有正常和功能受损 Fcγ 受体 IIB（FcγRIIB）变体的人源化小鼠，我们表明抑制性 Fcγ 受体是体内人类免疫系统体液免疫耐受的一个检查点。人 FcγRIIB 功能受损导致血清免疫球蛋白水平升高，产生不同的自身抗体特异性，以及体内人浆母细胞和浆细胞的比例增加。我们的结果表明，抑制性 FcγRIIB 可能是人类免疫系统体液免疫耐受的一个重要检查点。
